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Cancer-associated fibroblast-secreted CXCL16 attracts monocytes to promote stroma activation in triple-negative breast cancers

Author:
  • Roni Allaoui
  • Caroline Bergenfelz
  • Sofie Mohlin
  • Catharina Hagerling
  • Kiarash Salari
  • Zena Werb
  • Robin L. Anderson
  • Stephen P. Ethier
  • Karin Jirström
  • Sven Påhlman
  • Daniel Bexell
  • Balázs Tahin
  • Martin E. Johansson
  • Christer Larsson
  • Karin Leandersson
Publishing year: 2016-10-11
Language: English
Publication/Series: Nature Communications
Volume: 7
Document type: Journal article
Publisher: Nature Publishing Group

Abstract english

Triple-negative (TN) breast cancers (ER â ' PR â ' HER2 â ') are highly metastatic and associated with poor prognosis. Within this subtype, invasive, stroma-rich tumours with infiltration of inflammatory cells are even more aggressive. The effect of myeloid cells on reactive stroma formation in TN breast cancer is largely unknown. Here, we show that primary human monocytes have a survival advantage, proliferate in vivo and develop into immunosuppressive myeloid cells expressing the myeloid-derived suppressor cell marker S100A9 only in a TN breast cancer environment. This results in activation of cancer-associated fibroblasts and expression of CXCL16, which we show to be a monocyte chemoattractant. We propose that this migratory feedback loop amplifies the formation of a reactive stroma, contributing to the aggressive phenotype of TN breast tumours. These insights could help select more suitable therapies targeting the stromal component of these tumours, and could aid prediction of drug resistance.

Keywords

  • Cancer and Oncology

Other

Published
  • Cancer Immunology, Malmö
  • ISSN: 2041-1723
Sven Påhlman
E-mail: sven.pahlman [at] med.lu.se

Professor

Division of Translational Cancer Research

+46 46 222 64 21

MV406 312K1

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